Our research is focused on investigating the function and mechanism of action of novel lncRNAs in p53 signaling in colorectal cancer. We hypothesize that in response to DNA damage, select p53-regulated lncRNAs play a critical role in regulating a subset of the p53-regulated transcriptome to control cell survival and/or cell cycle arrest. As a first step towards achieving our goal, we have identified novel lncRNAs transactivated by p53 in multiple, p53-proficient colorectal cell lines. To examine their function, we use CRISPR/Cas9 to abolish their expression and for phenotypic studies. To determine their role in regulation the transcriptome, we employ gene expression profiling from candidate lncRNA-proficient and lncRNA-deficient cells in the presence or absence of DNA damage. In parallel, we perform lncRNA pulldowns to identify the factors bound by the candidate lncRNA. To examine the role of these lncRNAs in cancer pathogenesis we conduct experiments in colorectal cancer patient samples and in mice. We believe that these investigations will further our understanding of the function and mechanism of action of novel p53-regulated lncRNAs in the DNA damage response and their involvement in colorectal cancer.